Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBV4498)

• DOT Name: Tartrate-resistant acid phosphatase type 5 (ACP5)
• Synonyms: TR-AP; EC 3.1.3.2; Tartrate-resistant acid ATPase; TrATPase; Type 5 acid phosphatase
• Gene Name: ACP5
• Related Disease: Spondyloenchondrodysplasia with immune dysregulation
• UniProt ID: PPA5_HUMAN
• PDB ID: 1WAR; 2BQ8
• EC Number: 3.1.3.2
• Pfam ID: PF00149
• Sequence:
  MDMWTALLILQALLLPSLADGATPALRFVAVGDWGGVPNAPFHTAREMANAKEIARTVQI
  LGADFILSLGDNFYFTGVQDINDKRFQETFEDVFSDRSLRKVPWYVLAGNHDHLGNVSAQ
  IAYSKISKRWNFPSPFYRLHFKIPQTNVSVAIFMLDTVTLCGNSDDFLSQQPERPRDVKL
  ARTQLSWLKKQLAAAREDYVLVAGHYPVWSIAEHGPTHCLVKQLRPLLATYGVTAYLCGH
  DHNLQYLQDENGVGYVLSGAGNFMDPSKRHQRKVPNGYLRFHYGTEDSLGGFAYVEISSK
  EMTVTYIEASGKSLFKTRLPRRARP
• Function: Involved in osteopontin/bone sialoprotein dephosphorylation. Its expression seems to increase in certain pathological states such as Gaucher and Hodgkin diseases, the hairy cell, the B-cell, and the T-cell leukemias.
• KEGG Pathway:
  Riboflavin metabolism (hsa00740)
  Metabolic pathways (hsa01100)
  Lysosome (hsa04142)
  Osteoclast differentiation (hsa04380)
  Rheumatoid arthritis (hsa05323)
• Reactome Pathway: Vitamin B2 (riboflavin) metabolism (R-HSA-196843)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Spondyloenchondrodysplasia with immune dysregulation	DISER33V	Definitive	Autosomal recessive	[1]

14 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Tartrate-resistant acid phosphatase type 5 (ACP5).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Tartrate-resistant acid phosphatase type 5 (ACP5).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Tartrate-resistant acid phosphatase type 5 (ACP5).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Tartrate-resistant acid phosphatase type 5 (ACP5).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Tartrate-resistant acid phosphatase type 5 (ACP5).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Tartrate-resistant acid phosphatase type 5 (ACP5).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Tartrate-resistant acid phosphatase type 5 (ACP5).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Tartrate-resistant acid phosphatase type 5 (ACP5).	[9]
Beclomethasone dipropionate	DM5NW1E	Phase 4	Beclomethasone dipropionate decreases the activity of Tartrate-resistant acid phosphatase type 5 (ACP5).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Tartrate-resistant acid phosphatase type 5 (ACP5).	[11]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Tartrate-resistant acid phosphatase type 5 (ACP5).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Tartrate-resistant acid phosphatase type 5 (ACP5).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Tartrate-resistant acid phosphatase type 5 (ACP5).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Tartrate-resistant acid phosphatase type 5 (ACP5).	[15]

References

• [1] Spondyloenchondrodysplasia with spasticity, cerebral calcifications, and immune dysregulation: clinical and radiographic delineation of a pleiotropic disorder. Am J Med Genet A. 2006 Mar 15;140(6):541-50. doi: 10.1002/ajmg.a.31081.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [3] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [7] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [8] Decreased blood lead levels after calcitriol treatment in hemodialysis patients with secondary hyperparathyroidism. Bone. 2011 Dec;49(6):1306-10.
• [9] Epigenetic silencing of novel tumor suppressors in malignant melanoma. Cancer Res. 2006 Dec 1;66(23):11187-93. doi: 10.1158/0008-5472.CAN-06-1274.
• [10] Bone metabolism in children with asthma treated with inhaled beclomethasone dipropionate. J Pediatr. 1993 Feb;122(2):219-26.
• [11] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [12] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [13] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [14] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.